抄録
Cadmium (Cd) adversely affects a number of tissues, including kidney, liver, lung, pancreas, and testis. Especially, kidney and liver are thought to be primary target tissues of Cd. Recently, we have demonstrated that overaccumulation of p53 by Cd may relate to induction of apoptosis and may be due to the suppression of p53 degradation through inhibition of expressions of ubiquitin-conjugating enzyme genes, Ube2d family in rat proximal tubule cells (NRK-52E cells). In this study, we examined the effect of chronic exposure to Cd on the expressions of Ube2d family genes and accumulation of p53 in kidney and liver of mice. Five weeks old female C57BL/6J mice were fed diet containing 300 ppm Cd without restraint for 18 months. Every 6-month, we evaluated renal and hepatic toxicities, and measured mRNA levels of Ube2d family and protein levels of p53 in both tissues. Although renal toxicity was not remarkably developed until the 18-month exposure to Cd, significant decreases of mRNA levels of Ube2d family and accumulation of p53 were detected from the 6-month exposure to Cd in kidney. Hepatic toxicity was observed from the 6-month of Cd exposure and decrease of Ube2d mRNA levels by Cd was shown only in the group of exposure to Cd for 12 months. However, accumulation of p53 by Cd exposure was not detected in liver at all. These results suggest that with p53-dependent manner through inhibition of expressions of ubiquitin-conjugating enzyme genes, Cd causes renal toxicity rather than hepatic toxicity.
